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Liver injury is associated with severe coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of retrospective studies.
Parohan, M, Yaghoubi, S, Seraji, A
Hepatology research : the official journal of the Japan Society of Hepatology. 2020;50(8):924-935
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Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Coronavirus disease 2019 (COVID-19) can cause intestinal, respiratory, neuronal and hepatic diseases, and may lead to respiratory distress syndrome, organ failure, and even death in severe cases. The aim of this study was to assess the association between serum levels of Aspartate aminotransferase [enzyme], Alanine aminotransferase [enzyme], total Bilirubin [yellowish blood pigment] and Albumin [protein] with severity of COVID-19 infection. This study is a systemic review and meta-analysis of 20 retrospective studies conducted in China. The sample size of studies ranged from 21 to 651 patients (mean age, 53.3 years). Results indicate that high serum levels of aspartate aminotransferase, alanine aminotransferase, total bilirubin and lower serum levels of albumin are associated with a significant increase in the severity of COVID-19 infection. Authors conclude that attention should be paid to monitor the occurrence of liver dysfunction in patients with COVID-19 infection.
Abstract
The coronavirus disease 2019 (COVID-19) outbreak is a major threat to human beings. Lung injury has been reported as the major outcome of COVID-19 infection. However, liver damage has also been considered to occur in severe cases. The current meta-analysis of retrospective studies was carried out to summarize available findings on the association between liver injury and severity of COVID-19 infection. Online databases including PubMed, Scopus, Web of Science, and Cochrane Library were searched to detect relevant publications up to 1 April 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. Furthermore, publication bias test and sensitivity analysis were also applied. In total, 20 retrospective studies with 3428 COVID-19 infected patients (severe cases, n = 1455; mild cases, n = 1973), were included in this meta-analysis. Higher serum levels of aspartate aminotransferase (weighted mean difference, 8.84 U/L; 95% confidence interval [CI] 5.97 to 11.71; P < 0.001), alanine aminotransferase (weighted mean difference, 7.35 U/L; 95% CI, 4.77 to 9.93; P < 0.001), total bilirubin (weighted mean difference, 2.30 mmol/L; 95% CI, 1.24 to 3.36; P < 0.001), and lower serum levels of albumin (weighted mean difference, -4.24 g/L; 95% CI, -6.20 to -2.28; P < 0.001) were associated with a significant increase in the severity of COVID-19 infection. The incidence of liver injury, as assessed by serum analysis (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels), seems to be higher in patients with severe COVID-19 infection.
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Impact of dietary anthocyanins on systemic and vascular inflammation: Systematic review and meta-analysis on randomised clinical trials.
Fallah, AA, Sarmast, E, Fatehi, P, Jafari, T
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2020;135:110922
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Low-grade chronic inflammation contributes to the development of various chronic conditions like diabetes mellitus type2, chronic kidney disease, stroke, atherosclerosis, cardiovascular diseases, and cancer. Anthocyanins, a member of the flavonoid family, are water-soluble pigments that give plants their red-orange to blue-violet colours and have been shown to have antioxidant properties. The aim of this review and meta-analysis of 32 randomised controlled trials was to evaluate the impact of pure anthocyanins or anthocyanin-rich extracts/powders on inflammatory markers. The quality of studies for the meta-analysis was high for the inflammatory markers CRP (C-reactive protein), IL-6, TNF-alpha, adiponectin, and VCAM-1. There was a significant reduction in the pro-inflammatory CRP, IL-6, TNF-alpha and VCAM-1, and a significant increase in the anti-inflammatory adinopectin. Quality of studies was poor for other inflammatory markers evaluated. Higher doses tended to have a bigger positive effect. The authors conclude that anthocyanins may reduce inflammation.
Abstract
Anthocyanins are natural bioactive compounds that have several health benefits. This systematic review and meta-analysis assessed the impact of dietary anthocyanins on markers of systemic and vascular inflammation. Meta-analysis of 32 randomised controlled trials indicated that dietary anthocyanins significantly decreased levels of C-reactive protein (CRP; -0.33 mg/l, 95% CI: -0.55 to -0.11, P = 0.003), interleukin-6 (IL-6; -0.41 ρg/ml, 95% CI: -0.70 to -0.13, P = 0.004), tumor necrosis factor-alpha (TNF-α; -0.64 ρg/ml, 95% CI: -1.18 to -0.09, P = 0.023), intercellular adhesion molecule-1 (-52.4 ng/ml, 95% CI: -85.7 to -19.1, P = 0.002), and vascular adhesion molecule-1 (VCAM-1; -49.6 ng/ml, 95% CI: -72.7 to -26.5, P < 0.001) while adiponectin level was significantly increased (0.75 μg/ml, 95% CI: 0.23 to 1.26, P = 0.004). The levels of interleukin-1β (IL-1β; -0.45 ρg/ml, 95% CI: -3.77 to 2.88, P = 0.793) and P-selectin (-6.98 ng/ml, 95% CI: -18.1 to 4.15, P = 0.219) did not significantly change. Subgroup analyses showed that administration of higher doses of anthocyanins (>300 mg/day) significantly decreased levels of CRP, IL-6, TNF-α, and VCAM-1. The results indicate that dietary anthocyanins reduce the levels of systemic and vascular inflammation in the subjects.
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3.
Postprandial Reactive Hypoglycemia.
Altuntaş, Y
Sisli Etfal Hastanesi tip bulteni. 2019;53(3):215-220
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Reactive hypoglycaemia (RH) is a condition where blood sugar levels drop too low 2-5 hours after eating. There are 3 types of RH, depending on the time course: 1. Alimentary: within the first 2 hours, 2. Idiopathic: at around 3 hours and 3. Late: around 4-5 hours, after eating. RH is tightly connected with insulin secretions. Insulin is released in 2 phases, a rapid initial release within 10 minutes of eating, and a slow release over 24 hours. Alimentary RH is usually due to rapid gastric emptying, for example after bariatric surgery (surgery for weight loss resulting in a smaller stomach volume). This leads to rapid increase in blood glucose triggering an increased insulin secretion which in turn leads to hypoglycaemia. Idiopathic RH is most commonly seen in teenagers and lean people and is not thought to be a risk factor for developing type 2 diabetes. The causes are not clear. Late RH is due to a decreased first phase insulin release which leads to increased blood glucose levels which in turn trigger an excessive late phase insulin secretion. Over time this can lead to reduced insulin sensitivity and is a risk factor for developing type 2 diabetes. This review discusses the underlying physiological imbalances and reactive hypoglycaemia as a risk factor for developing type 2 diabetes in detail.
Abstract
Reactive hypoglycemia (RH) is the condition of postprandially hypoglycemia occurring 2-5 hours after food intake. RH is clinically seen in three different forms as follows: idiopathic RH (at 180 min), alimentary (within 120 min), and late RH (at 240-300 min). When the first-phase insulin response decreases, firstly, blood glucose starts to rise after the meal. This leads to late but excessive secretion of the second-phase insulin secretion. Thus, late reactive hypoglycemia occurs. Elevated insulin levels also cause down-regulation of the insulin post-receptor on the muscle and fat cells, thus decreasing insulin sensitivity. The cause of the increase in insulin sensitivity in IRH at 3 h is not completely clear. However, there is a decrease in insulin sensitivity in late reactive hypoglycaemia at 4 or 5 hours. Thus, patients with hypoglycemia at 4 or 5 h who have a family history of diabetes and obesity may be more susceptible to diabetes than patients with hypoglycemia at 3 h. We believe that some cases with normal glucose tolerance in OGTT should be considered as prediabetes at <55 or 60 mg/dl after 4-5 hours after OGTT. Metformin and AGI therapy may be recommended if there is late RH with IFG. Also Metformin, AGİ, TZD, DPP-IVInhibitors, GLP1RA therapy may be recommended if there is late RH with IGT. As a result, postprandial RH (<55 or 60 mg/dl), especially after 4 hours may predict diabetes. Therefore, people with RH along with weight gain and with diabetes history in the family will benefit from a lifestyle modification as well as the appropriate antidiabetic approach in the prevention of diabetes.
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Fermented Foods: Definitions and Characteristics, Impact on the Gut Microbiota and Effects on Gastrointestinal Health and Disease.
Dimidi, E, Cox, SR, Rossi, M, Whelan, K
Nutrients. 2019;11(8)
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Fermented foods have grown in popularity due to their proposed health benefits but there is limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health. This review paper looks at non-dairy fermented foods which have been studied in at least one RCT: kefir, sauerkraut, natto, and sourdough bread. The health benefits are attributed to the high ratio of probiotic microorganisms, metabolites, or ability to convert compounds into active metabolites, as well as prebiotics and vitamins contained in these foods. Kimchi has the greatest evidence from epidemiological and case control studies investigating risk of gastric cancers. Different food composition of kimchi is shown to both increase and decrease risks, whilst it had no impact on H. pylori levels. There were no studies on kefir in functional bowel disorders however, it was shown to help lactose malabsorption and reduce H. pylori levels. A small RCT on Sauerkraut showed it reduced IBS severity in patients and increased in vitro activity of key liver and kidney detoxifying enzymes. There are small pockets of data that show that tempeh may influence gut microbiota in humans, and that natto may increase bifidobacterial and short-chain fatty acids in healthy volunteers. There are numerous limited cohort studies on miso and cancer risk but no studies on gastrointestinal conditions. Finally, sourdough was shown to reduce FODMAPS and be better tolerated in IBS patients, reducing bloating, nausea and discomfort. Overall, all the studies provide insufficient evidence on fermented foods and gastrointestinal health.
Abstract
Fermented foods are defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. In recent years, fermented foods have undergone a surge in popularity, mainly due to their proposed health benefits. The aim of this review is to define and characterise common fermented foods (kefir, kombucha, sauerkraut, tempeh, natto, miso, kimchi, sourdough bread), their mechanisms of action (including impact on the microbiota), and the evidence for effects on gastrointestinal health and disease in humans. Putative mechanisms for the impact of fermented foods on health include the potential probiotic effect of their constituent microorganisms, the fermentation-derived production of bioactive peptides, biogenic amines, and conversion of phenolic compounds to biologically active compounds, as well as the reduction of anti-nutrients. Fermented foods that have been tested in at least one randomised controlled trial (RCT) for their gastrointestinal effects were kefir, sauerkraut, natto, and sourdough bread. Despite extensive in vitro studies, there are no RCTs investigating the impact of kombucha, miso, kimchi or tempeh in gastrointestinal health. The most widely investigated fermented food is kefir, with evidence from at least one RCT suggesting beneficial effects in both lactose malabsorption and Helicobacter pylori eradication. In summary, there is very limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health and disease. Given the convincing in vitro findings, clinical high-quality trials investigating the health benefits of fermented foods are warranted.
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A Review of Dietary (Phyto)Nutrients for Glutathione Support.
Minich, DM, Brown, BI
Nutrients. 2019;11(9)
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Glutathione is made up of 3 amino acids (cysteine, glutamic acid and glycine) and plays important roles in the body, including oxidative stress reduction, supporting the immune system and contributing to detoxification processes. Evidence suggests that it is an important marker and target for treatment in many chronic, age-related diseases. This review article explores the evidence of nutritional strategies to improve glutathione status. The authors examine the evidence for supplementation of the precursors of glutathione as well as with various forms of supplemental glutathione itself, and the impacts on glutathione status and clinical impacts. Crucially, the review article provides information on dietary sources of precursors of glutathione and glutathione itself, which will provide Nutrition Practitioners with compelling information for use in clinic. Lean protein, brassica vegetables, polyphenol-rich fruits and vegetables, green tea, herbs and spices and omega-3 rich foods are all discussed in detail.
Abstract
Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.
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Vitamin D Supplementation in Central Nervous System Demyelinating Disease-Enough Is Enough.
Häusler, D, Weber, MS
International journal of molecular sciences. 2019;20(1)
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Vitamin D is associated with a reduced risk and severity of multiple sclerosis (MS). However, whether supplementing vitamin D level alters disease severity, is a matter of ongoing debate. This review looks at both clinical and pre-clinical evidence for supplementing vitamin D in people with MS. In vitro experiments show that vitamin D and its metabolites can alter function of various immune cells, mostly via interaction with vitamin D receptors (VDR). Results from human clinical trials, however, are mixed. Preclinical evidence suggests that high dose vitamin D supplementation, when leading to hypercalcaemia, a potentially serious side effect of excessive vitamin D intake, may worsen MS. The authors also review research which suggests mechanisms by which sun exposure can improve MS symptoms independent of vitamin D production. The authors conclude that moderate sun exposure, combined with adequate dietary intake of vitamin D, and in conjunction with a regular assessment of vitamin D serum levels (to avoid hypercalcaemia), might be the best strategy for patients with MS.
Abstract
The exact cause of multiple sclerosis (MS) remains elusive. Various factors, however, have been identified that increase an individual's risk of developing this central nervous system (CNS) demyelinating disease and are associated with an acceleration in disease severity. Besides genetic determinants, environmental factors are now established that influence MS, which is of enormous interest, as some of these contributing factors are relatively easy to change. In this regard, a low vitamin D status is associated with an elevated relapse frequency and worsened disease course in patients with MS. The most important question, however, is whether this association is causal or related. That supplementing vitamin D in MS is of direct therapeutic benefit, is still a matter of debate. In this manuscript, we first review the potentially immune modulating mechanisms of vitamin D, followed by a summary of current and ongoing clinical trials intended to assess whether vitamin D supplementation positively influences the outcome of MS. Furthermore, we provide emerging evidence that excessive vitamin D treatment via the T cell-stimulating effect of secondary hypercalcemia, could have negative effects in CNS demyelinating disease. This jointly merges into the balancing concept of a therapeutic window of vitamin D in MS.
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Role of Probiotics in Non-alcoholic Fatty Liver Disease: Does Gut Microbiota Matter?
Xie, C, Halegoua-DeMarzio, D
Nutrients. 2019;11(11)
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Non-alcoholic fatty liver disease (NAFLD) is characterised by an excessive accumulation of fat in the liver tissue, without excessive alcohol consumption, and appears to be related to metabolic syndrome. It is thought to have a prevalence of 25% globally and there are no pharmacological treatments available. This review discusses the connection between the gut microbiota (GM) and NAFLD. Various mechanisms by which the GM may be involved in the development of NAFLD are discussed. As probiotics and prebiotics can normalise GM and reverse dysbiosis their use may benefit patients with NAFLD. This has been confirmed in animal models. The authors review 26 randomised controlled trials (RCTs) of probiotics and/or prebiotics in the treatment of NAFLD which evaluate biochemical markers, as well as five meta-analyses, and found that overall there is strong evidence that probiotics and/or prebiotics can lower ALT and AST (markers of NAFLD), although results for other biochemical markers were mixed. They also reviewed RCTs assessing NAFLD by imaging and histological means, and again found benefits from probiotic and/or prebiotic supplementation.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid metabolism and influences the balance between pro/anti-inflammatory effectors in the liver. Although studies reveal the association between GM dysbiosis and NAFLD, decoding the mechanisms of gut dysbiosis resulting in NAFLD remains challenging. The potential pathophysiology that links GM dysbiosis to NAFLD can be summarized as: (1) disrupting the balance between energy harvest and expenditure, (2) promoting hepatic inflammation (impairing intestinal integrity, facilitating endotoxemia, and initiating inflammatory cascades with cytokines releasing), and (3) altered biochemistry metabolism and GM-related metabolites (i.e., bile acid, short-chain fatty acids, aromatic amino acid derivatives, branched-chain amino acids, choline, ethanol). Due to the hypothesis that probiotics/synbiotics could normalize GM and reverse dysbiosis, there have been efforts to investigate the therapeutic effect of probiotics/synbiotics in patients with NAFLD. Recent randomized clinical trials suggest that probiotics/synbiotics could improve transaminases, hepatic steatosis, and reduce hepatic inflammation. Despite these promising results, future studies are necessary to understand the full role GM plays in NAFLD development and progression. Additionally, further data is needed to unravel probiotics/synbiotics efficacy, safety, and sustainability as a novel pharmacologic approaches to NAFLD.
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The Fluid Aspect of the Mediterranean Diet in the Prevention and Management of Cardiovascular Disease and Diabetes: The Role of Polyphenol Content in Moderate Consumption of Wine and Olive Oil.
Ditano-Vázquez, P, Torres-Peña, JD, Galeano-Valle, F, Pérez-Caballero, AI, Demelo-Rodríguez, P, Lopez-Miranda, J, Katsiki, N, Delgado-Lista, J, Alvarez-Sala-Walther, LA
Nutrients. 2019;11(11)
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The Mediterranean diet is considered one of the most studied diets in scientific literature and this review specifically looks at two fluid aspects of the MedDiet; olive oil and red wine. Olive oil is rich in phenolic compounds and red wine in polyphenols and the study looks at their therapeutic effect on cardiovascular disease prevention, particularly on lipids, blood pressure, plaque and glucose metabolism. Known mechanisms of the MedDiet include reduction of inflammatory and oxidative stress markers, and an improvement in lipid profile and insulin sensitivity. Polyphenols are important antioxidants abundant in plant foods including olives and red grapes used in wine (known to be x10 richer in polyphenols than white wine). The review reports that low to moderate consumption of red wine 30-50g daily lowers risk factors for CVD, improve HDL lipid profile, exerts a beneficial effect on blood pressure (BP), promotes vasodilation thus helping to reduce plaques and finally limited data shows it may beneficially affect insulin resistance. Polyphenols in olives were reported to reduce blood pressure, reduce LDL lipids and increase HDL lipids, support weight loss and help prevent obesity, metabolic syndrome and type II diabetes, reduce inflammation and oxidative stress, and possibility benefit gut microbiota. The review concludes that both fluids exert cardio-protection when consumed in moderation as part of a MedDiet.
Abstract
A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism.
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Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review.
Martín-Masot, R, Nestares, MT, Diaz-Castro, J, López-Aliaga, I, Alférez, MJM, Moreno-Fernandez, J, Maldonado, J
Nutrients. 2019;11(11)
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Anaemia is a common clinical expression of Celiac Disease (CD) alongside vitamin B12, iron and folate deficiencies. This review looks at the latest evidence and effects of a gluten free diet, the mainstay of treatment for CD. Typically, symptoms subside whilst adhering to a GF diet however in 20% of people anaemia and nutrient deficiencies can persist. Some of this is attributed to lack of adherence to the diet, oftentimes accidental given the wide range of foods containing gluten. This in turn leads to further damage of the intestine and can be difficult to detect and monitor effectively. Inflammation of the gastrointestinal tract, and malabsorption, are the main reasons for nutrient deficiencies leading to anaemia in CD. Iron is a critical nutrient which can easily be affected by damage to the intestinal villi, common in CD, and over time lead to iron deficiency anaemia as the body is unable to absorb dietary iron and the body’s iron stores are depleted. Likewise, absorption of vitamins B12 and B9 (folate) are also impaired by damaged villi and vitamin B12 is further affected by small intestine injuries including decreased gastric acid production, bacterial overgrowth and reduced intrinsic factor efficiency. Deficiencies of these two nutrients can lead to macrocytic anaemia with low blood cell volumes. Overall a gluten free diet is shown to reduce symptoms of CD in a matter of weeks. The more patients adhere to the diet, the more the risk of nutrient deficiencies and anaemia reduces.
Abstract
Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.
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Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.
Patrick, RP
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019;33(2):1554-1564
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Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by progressive memory loss, spatial disorientation, cognitive impairment and behavioural changes. Ageing is the main risk factor for AD, with approximately one-third of Americans over the age of 85 being affected by the condition. The APOE gene provides instructions for making the apolipoprotein E family of proteins that are involved in fat metabolism and cholesterol transport. There are three different variants of this gene, one inherited from each parent. The variant called APOE4 is thought to increase AD risk from 2-3-fold (one inherited copy) to as much as 15-fold (two inherited copies), compared to individuals who do not carry this variant. The omega-3 oil docosahexaenoic acid (DHA) is an essential fatty acid, which comprises approximately 30% of the fats found in the human brain. Low levels of DHA in the brain increase the risk of developing AD, while normal and high levels may prevent the condition and ameliorate symptoms. This review paper brings together several lines of evidence on why individuals with the APOE4 gene variant don’t respond well to DHA supplementation but experience positive effects from dietary intake of DHA. The author suggests that this is due to the different forms of DHA found in dietary and supplemental sources. Some of the DHA present in fish and seafood is in phospholipid form, which is metabolised into lysophosphatidylcholine DHA (DHA-lysoPC) in the body. In contrast, fish oil supplements contain no DHA in phospholipid form, but in other forms that are mostly metabolised to free DHA. This paper puts forward an argument that, due to the breakdown of the integrity of the blood-brain barrier, APOE4 carriers have impaired brain transport of free DHA but not DHA-lysoPC. The author concludes that dietary sources that contain high amounts of DHA in phospholipid form, such as fish and fish roe may help increase plasma levels of DHA-lysoPC, which may be better transported to the brains of APOE4 carriers. She also highlights the pressing need for future clinical trials to evaluate the effects of omega-3 oils in phospholipid form on the cognitive function of APOE4 carriers with AD.
Abstract
Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood-brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the risk of AD.-Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.